Water-soluble lipopolymer delivery of N-methyl-D-aspartic acid receptor 2B siRNA relieves chronic neuropathic pain in rats

Jianhua Lu, Yuanxiang Tao, Xue Yang, Weifeng Tu, Hao Chen, Jiaxiang Xiong, Chungui Hu

Research output: Contribution to journalArticle

Abstract

Spinal dorsal horn N-Methyl-D-aspartic acid receptor 2B (NR2B) overexpression plays an important role in the production and maintenance of neuropathic pain. Because small interfering RNA (siRNA) can inhibit NR2B expression, siRNA may provide a novel approach to treat neuropathic pain and possibly nerve injury. However, an efficient and safe vector for NR2B siRNA has not been discov- ered. This study shows that a water soluble lipopolymer (WSLP) comprised of low molecular weight polyethyleneimine (PEI) and cholesterol can deliver siRNA targeting NR2B for the treatment of neuropathic pain. Results show that intrathecal injection of WSLP/siRNA complexes for 3 days in- hibit NR2B gene expression with reductions in mRNA and protein levels by 59% and 54%, respec- tively, compared with control rats (P < 0.01). Injection of WSLP complexed with scrambled siRNA, or PEI with siRNA did not show this inhibitory effect. Moreover, injection of WSLP/siRNA complexes significantly relieved neuropathic pain at 3, 7, 12, and 21 days, while injection of WSLP with scrambled siRNA or PEI with siRNA did not. These results demonstrate that WSLP can efficiently deliver siRNA targeting NR2B in vivo and relieve neuropathic pain.

Original languageEnglish (US)
Pages (from-to)2279-2283
Number of pages5
JournalNeural Regeneration Research
Volume6
Issue number29
DOIs
StatePublished - Nov 25 2011

Keywords

  • N-Methyl-D-aspartic acid receptor 2B
  • Neuropathic pain
  • Peripheral nerve injury
  • Small interfering RNA
  • Water soluble lipopolymer

ASJC Scopus subject areas

  • Developmental Neuroscience

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